Electrotransport devices and transdermal patches are drug delivery systems that are capable of satisfying many needs facing the health care industry. For example, attempts have been made to control and increase the rate of delivery, reduce drug and agent degradation, and reduce the risk of infection. However, such goals have become more difficult to reach as the molecular size of the drugs and therapeutic agents to be delivered increases. Such drugs and agents include peptides, polypeptides and proteins.
An electrotransport device generally includes at least two electrodes and a source of electrical power. Each electrode is in electrical communication and physical contact with some portion of the skin, nails, mucus membrane or other membrane surface of the body. One electrode is generally referred to as the active or donor electrode, and the other electrode is referred to as the counter or return electrode. The donor electrode also includes a donor reservoir which contains the drug or therapeutic agent to be delivered, and the counter electrode includes a counter reservoir that generally contains an electrolyte. In combination, the electrodes close the electrical circuit through the patients body surface.
The drug or therapeutic agent is a charged molecule, or ion, that is carried through the body surface by applied current. The charge of the drug or agent determines whether the donor electrode is the cathode or anode. For example, the donor electrode is the anode when the drug is positively charged, and the counter electrode is the cathode. Alternatively, the donor electrode is the cathode when the drug is negatively charged, and the counter electrode is the anode.
The reservoirs are generally in the form of a pouch, a cavity, a porous sponge or pad, or a pre-formed gel or polymer composite body. The donor reservoir is in electrical communication with the respective electrode. Semipermeable membranes typically have a limited number of minute pores to control the rate of drug delivery.
Known electrotransport devices may also include a semipermeable membrane that controls the rate of drug delivery. The membrane is located between the donor reservoir and the body surface. The membrane is also in electrical and ion-transmitting communication with the donor reservoir and the body surface. Membranes are also used in the counter reservoir to control passive delivery of a drug or therapeutic agent.
However, there may be a need for a semipermeable membrane that more accurately and precisely controls passive drug/agent flux. Prior membranes were disadvantaged in that membranes having small pore size (about 0.09 micron diameter) and low porosity (about 4.times.10.sup.5 pathways per cm.sup.2 or 0.003% by volume) prevented passive flux, but failed to allow therapeutically sufficient current after lamination and assembly. Prior devices are also disadvantaged in that the membrane can be damaged or compromised by oils and other contaminants from the skin or drug reservoir during operation of the device. The contamination may cause occlusions in the membrane that affect the rate of drug delivery. For example, if the membrane loses resistance, the drug may passively flux into the body surface at significant levels. Membranes may also have excessive resistance that hampers drug delivery reducing efficacy and depleting the electrical power source. Such losses of control over the rate of drug delivery are acutely disadvantageous where the drug is an analgesic, such as an opioid.
Membrane pores may also be deleteriously affected when the membrane is contacted with the body surface. Body oils, dirt particulates and other contaminates on the skin are transferred to the semipermeable membrane clogging pores in the membrane. Hydrophobic components in the donor and/or counter reservoirs may also clog membrane pores or cause occlusions. Such damage to the semipermeable membrane compromises control, precision and accuracy of the drug delivery rate.
Prior devices are further disadvantageous because the membrane pores may be altered when the membrane is affixed to the donor and/or counter reservoir. Semipermeable membranes are affixed using adhesives and/or laminates under heat and/or pressure that can cause occlusions in and deformation of the membrane pores. Such damage deleteriously affects the passive and/or iontophoretic flux of the drug/agent.